As a subtype of an adenosine receptor, A1, A2a, A2b and A3 are known. Adenosine exhibits tracheostenotic action to an asthma patient and, on the other hand, theophylline which is an agent for treating asthma exhibits adenosine antagonism. In addition, it has been recently shown that the activation of A3 receptor in a rat causes degranulation from mast cells (Journal of Biological Chemistry, vol. 268, 16887–16890, 1993), and that A3 receptor is present on eosinophils in peripheral blood and its stimulation activates phospholipase C (PLC) to increase the intracellular calcium concentration (Blood, vol. 88, 3569–3574, 1996).
In addition, cytokines such as TNF-α (tumor necrosis factor-α), IL-1 (interleukin-1) and the like are biological substances which are produced by a variety of cells such as monocyte or macrophage in response to the infection and other cellular stress (Koj, A., Biochim. Biophys. Acta, 1317, 84–94 (1996)). Although these cytokines play an important role in the immune response when they are present at an appropriate amount, it is thought that the overproduction is associated with a variety of inflammatory diseases (Dinarello, C. A., Curr. Opin. Immunol., 3, 941–948 (1991)). p38 MAP kinase which was cloned as a homologue of MAP kinase is associated with the control of production of these cytokines and signal transduction system coupled with a receptor and there is a possibility that the inhibition of p38 MAP kinase becomes a drug for treating inflammatory diseases (Stein, B., Anderson, D., Annual Report in Medicinal Chemistry, edited by Bristol, J. A., Academic Press, vol. 31, pages 289–298, 1996).
Hitherto, as a compound exhibiting the selective antagonism for adenosine A3 receptor, xanthine derivatives are reported in GB-A-2288733 and WO 95/11681 and the following compounds are reported in Journal of Medicinal Chemistry, vol. 40, 2596–2608, 1997:

In addition, in WO 97/33879, there are described an adenosine A3 receptor antagonistic agent containing a compound represented by the formula:
wherein R represents hydrogen, chlorine, bromine, fluorine, iodine, hydroxy, C1-4 alkyl, C1-4 alkoxy or C1-4 alkylcarboxy, or a salt thereof and, more specifically, a compound
is described.
In addition, as a compound having a p38 MAP kinase inhibitory action, imidazole derivatives are described in JP-T 7-50317 (WO 93/14081) and oxazole derivatives are described in JP-T 9-505055 (WO 95/13067), respectively.
On the other hand, as thiazole compounds, the following compounds are known:
1) 1,3-thiazole derivatives represented by the formula:
wherein R1 represents a cycloalkyl group, a cyclic amino group, an amino group optionally having, as a substituent, 1 or 2 lower alkyl, phenyl, acetyl or lower alkoxycarbonylacetyl, an alkyl group optionally having, as a substituent, hydroxyl, carboxyl or lower alkoxycarbonyl, or a phenyl group optionally having, as a substituent, carboxyl, 2-carboxyethenyl or 2-carboxy-1-propenyl, R2 represents a pyridyl group optionally having, as a substituent, lower alkyl, R3 represents a phenyl group optionally having, as a substituent, lower alkoxy, lower alkyl, hydroxyl, halogen or methylenedioxy, or salts thereof, which have analgesic, antipyretic, anti-inflammatory, anti-ulcerative, thromboxane A2 (TXA2) synthesizing enzyme-inhibitory, and platelet coagulation-inhibitory activities (JP-A 60-58981),2) 1,3-thiazole derivatives represented by the formula:
wherein R1 represents an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a cycloalkyl group, a heterocyclic group employing carbon as an attachment point or an amino group optionally having substituents, R2 represents a pyridyl group optionally substituted with an alkyl group, R3 represents a phenyl group optionally having substituents, or salts thereof, which have analgesic, antipyretic, anti-inflammatory, anti-ulcerative, TXA2 synthesizing enzyme-inhibitory, and platelet coagulation-inhibitory activities (JP-A 61-10580),3) 1,3-thiazole derivatives represented by the formula:
wherein R1 represents an alkyl group, an alkenyl group, an aryl group, an aralkyl group, a cycloalkyl group, a heterocyclic group employing carbon as an attachment point or an amino group optionally having substituents, R2 represents a pyridyl group optionally substituted with an alkyl group, R3 represents an aryl group optionally having substituents, or salts thereof, which have analgesic, antipyretic, anti-inflammatory, anti-ulcerative, TXA2 synthesizing enzyme-inhibitory, and platelet coagulation-inhibitory activities (U.S. Pat. No. 4,612,321),4) imidazole derivatives represented by the formula:
which have an anti-cancer activity and a cytokine inhibitory activity, more specifically, the following compounds are described (WO 97/12876):

Since an adenosine A3 antagonist, a p38 MAP kinase inhibiting agent and a TNF-α production-inhibiting agent having the satisfactory activity and effect, safety, (oral) absorption, (metabolism) stability and the like have not been found, it is desired the development of the excellent adenosine A3 receptor antagonist, the p38 MAP kinase-inhibiting agent and the TNF-α production-inhibiting agent as a pharmaceutical which are effective for preventing or treating adenosine A3 receptor-related diseases, cytokine-mediated diseases and the like.